Predictors of New-Onset Diabetes in Patients Treated With Atorvastatin: Results From 3 Large Randomized Clinical Trials

doi:10.1016/j.jacc.2010.10.047

Journal of the American College of Cardiology

Volume 57, Issue 14, 5 April 2011, Pages 1535-1545

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Objectives

We sought to examine the incidence and clinical predictors of new-onset type 2 diabetes mellitus (T2DM) within 3 large randomized trials with atorvastatin.

Background

Statin therapy might modestly increase the risk of new-onset T2DM.

Methods

We used a standard definition of diabetes and excluded patients with prevalent diabetes at baseline. We identified baseline predictors of new-onset T2DM and compared the event rates in patients with and without new-onset T2DM.

Results

In the TNT (Treating to New Targets) trial, 351 of 3,798 patients randomized to 80 mg of atorvastatin and 308 of 3,797 randomized to 10 mg developed new-onset T2DM (9.24% vs. 8.11%, adjusted hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 0.94 to 1.29, p = 0.226). In the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial, 239 of 3,737 patients randomized to atorvastatin 80 mg/day and 208 of 3,724 patients randomized to simvastatin 20 mg/day developed new-onset T2DM (6.40% vs. 5.59%, adjusted HR: 1.19, 95% CI: 0.98 to 1.43, p = 0.072). In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial, new-onset T2DM developed in 166 of 1,905 patients randomized to atorvastatin 80 mg/day and in 115 of 1,898 patients in the placebo group (8.71% vs. 6.06%, adjusted HR: 1.37, 95% CI: 1.08 to 1.75, p = 0.011). In each of the 3 trials, baseline fasting blood glucose, body mass index, hypertension, and fasting triglycerides were independent predictors of new-onset T2DM. Across the 3 trials, major cardiovascular events occurred in 11.3% of patients with and 10.8% of patients without new-onset T2DM (adjusted HR: 1.02, 95% CI: 0.77 to 1.35, p = 0.69).

Conclusions

High-dose atorvastatin treatment compared with placebo in the SPARCL trial is associated with a slightly increased risk of new-onset T2DM. Baseline fasting glucose level and features of the metabolic syndrome are predictive of new-onset T2DM across the 3 trials.

Key Words

diabetes

low-density lipoprotein (LDL) cholesterol

statin

Abbreviations and Acronyms

BMI

body mass index

confidence interval

HDL

high-density lipoprotein

hazard ratio

LDL

low-density lipoprotein

myocardial infarction

T2DM

type 2 diabetes mellitus

Cited by (0)

: The TNT, IDEAL, and SPARCL trials were funded by Pfizer, Inc. The SPARCL Steering Committee approved the use of SPARCL trial data for this analysis, but interpretation and conclusions contained herein do not necessarily represent the position of the committee. Dr. Waters has consulted for Anthera, Aegerion, Cortria, CSL, Genentech, Pfizer, and Roche; received honoraria from Bristol-Myers Squibb and Pfizer; participated in clinical trials sponsored by Biosante, Merck Schering-Plough, Pfizer, and Roche; and owns stock options in Anthera. Dr. Kastelein receives lecture fees from Pfizer and sits on the IDEAL Steering Committee. Dr. Colhoun receives research funding from and is on the Speakers' Bureau for Pfizer. Dr. Barter has consulted for AstraZeneca, CSL, Merck, Pfizer, Roche, and Sanofi-Aventis; received honoraria from Abbott, AstraZeneca, Merck, Pfizer, and Roche; and participated in clinical trials sponsored by AstraZeneca, Merck, Pfizer, and Roche. Drs. DeMicco, Breazna, and Wun are Pfizer employees. All other authors have reported that they have no relationships to disclose.